Platelet-derived growth factor B-chain gene expression in mesangial cells : effect of phorbol ester on gene transcription and mRNA stability .

Bhandari B ; Woodruff K ; Abboud HE

Department of Medicine , University of Texas Health Science Center at San Antonio .

Mol Cell Biochem 140 : 31-6 ( 1994)

Abstract
We have investigated the effect of phorbol 12-myristate 13-acetate ( PMA ) on platelet-derived growth factor ( PDGF ) B-chain gene transcription as well as on mRNA stability in cultured human mesangial cells . Addition of actinomycin to cells stimulated with PMA decreases steady state levels of PDGF-B chain mRNA analysed by solution hybridization assay . PDGF-B chain gene transcription was also assayed directly by measuring elongation of transcripts in isolated nuclei followed by hybridization of labeled RNA transcripts to a cDNA encoding for PDGF-B chain . Our data show that PMA induces PDGF-B chain gene transcription by approximately 2-fold . alpha-Amanitin , an RNA polymerase II inhibitor , blocked transcription by more than 70% . In addition , we determined the effect of PMA on the halflife of PDGF-B chain mRNA directly by pulse chase method . In human mesangial cells , the PDGF-B chain mRNA exhibited halflife of approximately 105 min. In the presence of PMA , the halflife of PDGF-B chain mRNA was reduced to approximately min. These studies indicate that regulation of PDGF-B chain gene by PMA in human mesangial cells involves a coordinate effort at the level of transcription and mRNA stability .